A pilot study evaluating the plasma prolactin (PRL) response to 0.5 mg I.M. reserpine in unmedicated chronic schizophrenic males (N=7) in comparison to normal males (N=8) indicated that the PRL response was significantly decreased in the schizophrenic group. Furthermore, all the schizophrenics had lower PRL response than that of any normal subject. Thus, the PRL response to reserpine may be a useful diagnostic tool in discriminating schizophrenics from normals. The major goals of this project are (1) to study a larger sample of chronic schizophrenic males (N=20), and normal males (N=20), to replicate the original findings, (2) to determine if schizophrenic males differ from a non-schizophrenic patient control group, endogenously depressed males (N=20) and (3) to evaluate whether these findings extend to subchronic schizophrenic males (N=20). If the findings are replicated and if schizophrenics also differ from depressed patients, future work will evaluate other groups of schizophrenics, females (with focus upon the effect of menopausal status and phase of the menstrual cycle) and other diagnostic groups. If the PRL response to reserpine proves to be an important diagnostic test in discriminating subjects with schizophrenia from subjects with other mental disorders, it will be an aid to researchers and clinicians. We will also determine if reserpine blood levels and/or tolerance in the PRL system in schizophrenics contributed to our pilot findings. This pilot data is the first neuroendocrine finding supporting the dopamine hypothesis; in particular, it suggests that chronic schizophrenics have excessive intraneuronal storage pool dopamine. If these findings are replicated, further research should investigate the role of intraneuronal storage dopamine in schizophrenia.